Prochiral carbons

In the asymmetric reduction of ketones, stereodifferentiation has been explained in terms of the steric recognition of two substituents on the prochiral carbon by chirally modified reducing agents40. Enantiomeric excesses for the reduction of dialkyl ketones, therefore, are low because of the little differences in the bulkiness of the two alkyl groups40. In the reduction of ketoxime ethers, however, the prochiral carbon atom does not play a central role for the stereoselectivity, and dialkyl ketoxime ethers are reduced in the same enantiomeric excess as are aryl alkyl ketoxime ethers. Reduction of the oxime benzyl ethers of (E)- and (Z)-2-octanone with borane in THF and the chiral auxiliary (1 R,2S) 26 gave (S)- and (R)-2-aminooctane in 80 and 79% ee, respectively39. 

The first example of asymmetric induction in transfer of chirality from the chiral sulfur atom to the prochiral carbon atom was described by Goldberg and Sahli in 1965 (197). It concerns the pyrolysis of the optically active p-tolyl tra s-4-methylcyclohexyl sulfoxides 258. It was found that on pyrolysis at 200 to 250°C, optically active sulfoxides (R)-258 and (5)-258 yield optically active 4-methylcyclohexenes-l 259, with the absolute R and S configurations, respectively, at the newly formed chiral carbon atoms (Scheme 25). The optical purities of the 4-methylcyclohexenes-l that were formed depended largely on the temperature of pyrolysis. Thus, the values of 42 and 70% optical purity were noted for 259 at 250° and 200°C, respectively. The formation of the cycloolefins 259, whose absolute configurations are the same as those of the starting optically active sulfoxides 258, indicates that the pyrolysis reaction proceeds... 

In molecules that contain a stereogenic centre, the NMR spectra can sometimes be more complex than would otherwise be expected. Groups such as -CH2- groups (or any -CX2- group such as -C(Me)2- or -CR2-) require particular attention in molecules which contain a stereogenic centre. The carbon atom of a -CX2- group is termed a prochiral carbon if there is a stereogenic centre (a chiral centre) elsewhere in the... 

The absence from a formula of any one of the horizontal or vertical lines at a chiral or prochiral carbon atom (as in examples on pages 27 and 32), or of or Z designations at double bonds, indicates that the configuration of that stereoisomeric centre is not known. Also, as in our previous document [2], the convention of orienting polymer structures (and the corresponding constitutional and configurational units) from left to right is used. Thus, the two bracketted constitutional units in... 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Problem 5.25 (a) What is the necessary and sufficient condition for the existence of enantiomers (6) What is the necessary and sufficient condition for measurement of optical activity (c) Are all substances with chiral atoms optically active and resolvable (d) Are enantiomers possible in molecules that do not have chiral carbon atoms (e) Can a prochiral carbon ever be primary or tertiary (/) Can conformational enantiomers ever be resolved ... 

It was pointed out over 60 years ago that the recognition of a chiral (or, as subsequently realized, a prochiral) carbon by an enzyme implies that at least three of the groups surrounding the carbon atom must interact with the enzyme. This is the multi-point attachment theory.4 If only two of the groups interact, the other two may be interchanged without affecting the binding of the substrate (structures 8.9). 

The generation of a chiral center as a result of alkene hydroformylation can take place either by formylation or hydride addition at the prochiral carbon (equations 30 and 31). Kinetic resolution in the hydroformylation reaction of a racemic alkene containing a chiral center could also occur, but in this example the chiral center is not generated as a result of the hydroformylation reaction. 

PLE) transforms the meso substrate into chiral compound 5 with >98% te. This en/yme is capable of differendating between the two enantiotopic ester groups on the prochiral carbon atom and hydrolyzing only one of them to a carboxylic acid. Maximum enan-tioselectivity is achieved by carrying out the reaction in 25% aqueous DMSO solution at 35 C. 

The chiral l,3-thiazolidine-2-thione (1) has been used to differentiate between two identical groups attached to a prochiral carbon atom, a distinction that has been limited to certain enzymes.3 Thus, the two ligands in the optically active diamide 2, prepared from 3-methylglutaric acid and 1, differ in their reactivity with amines, particularly cyclic secondary amines (Figure I). Reaction with piperidine results... 

The molecule in Figure I is an example of a prochiral molecule. The asymmetrical enzyme binds only to hydrogen a and not to hydrogen b due to the spatial arrangement of its active site with respect to the other substituents on the prochiral carbon. All known dehydrogenases are stereospecific in this manner. 

Table 6. Face of the unsaturated prochiral carbon atom preferably attacked by CO in 1-butene and styrene hydroformylation...

An alternative concept is asymmetric desymmetrization of a prochiral molecule of type 83. The starting materials 83 have three keto groups and one carbon atom bearing at least three substituents. A prerequisite is the presence of a prochiral carbon atom with two identical substituents bearing a keto functionality (Scheme 6.39, Eq. (2)). This type of asymmetric intramolecular aldol reaction proceeds with formation of cyclic ketols of type 84 with two stereogenic centers. Dehydration can subsequently be performed, leading to optically active enones of type 85. The two types of intramolecular aldol reaction are shown conceptually in Scheme 6.39. 

FIGURE 27.1 Diastereotopic transition states involved in the reaction of a prochiral carbon-centered radical with a chiral organotin hydride. 

Thus, for both chiral and prochiral a-olefins, the isotactic sequence of the stereogenic tertiary carbon atom of the backbone is due to the enantioselectivity of the chiral active sites to the prochiral carbon atom of the monomer. The stereoselectivity (namely the selection, among the enantiomers, of a racemic... 

This has the important effect of fixing the opposite of the initial chirality of the prochiral carbon. In other words Re and Si faces bonded to Rh generate S or R chirality, respectively. This is shown schematically in Fig. 9.4. The detailed... 

Asymmetric epoxidation The catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades. The non-racemic epoxides are prepared either by enantioselective oxidation of a prochiral carbon-carbon double bond or by enantioselective alkylidenation of a prochiral C=0 bond (e.g. via a ylide, carbene or the Darzen reaction). The Sharpless asymmetric epoxidation (SAE) requires allylic alcohols. The Jacobsen epoxidation (using manganese-salen complex and NaOCl) works well with ds-alkenes and dioxirane method is good for some trans-alkenes (see Chapter 1, section 1.5.3). 

For meio-inositols only, the C-1 locant is assigned to the (prochiral) carbon atom, which has the L-configuration (see Chapter 7). 

Fig. 5. Biosynthetic pathways for (I) 6-methylsalicylic acid and (II) the triacetic acid lactone. The structures of the intermediates have not been identified. The stereochemical course of the prochiral carbons (C-2 and C-4 in the triketide intermediate, C-3 and C-5 in 6-MSA) was investigated using R)- and (S)- [l- C,2- H]malonic acid extender substrate analogs in a coupled assay with 6-MSAS and succinyl-CoA transferase. The distinguishable hydrogens originating from the chiral malonyl CoA are labeled with H and H. Triacetic acid lactone synthesis is catalyzed by 6-MSAS in the absence NADPH...

MSA does not contain any chiral carbon centers. Before the aromatization of the six-membered ring occurs, two prochiral carbons (C-2 and C-4 in the six-carbon intermediate) evolve, each of which loses a hydrogen in the process of the dehydratization/aromatization steps. In addition, C-3 of the six-carbon intermediate forms a chiral center when the ketone is reduced to a hydroxyl by a ketoreductase activity (Fig. 5). The chirality of this hydroxyl carbon is unclear since the intermediate has not been isolated. It is also unknown if this carbon retains its chirality in an eight-carbon intermediate or whether the hydroxyl is eliminated by dehydration prior to the third condensation reaction. The stereospecificity at the prochiral C-2 and C-4 carbons in the reaction intermediates was addressed using chemically synthesized (] )- and (S)-[1- C, 2- H]malonate precursors which were enzymatically converted into CoA derivatives via succinyl CoA transferase [127,128]. Thus, the prochiral methylene in malonyl CoA was replaced by chiral, double-labeled (S)- or (J )-[1- C, 2- H]malonyl CoA substrates in the reaction mixture with 6-MSAS. The condensation is expected to occur with inversion of configuration and the intact methylene... 

Sakai and co-workers [38] studied the additions to conjugate esters protected with a cyclic diol as a chiral auxiliary. The ester is protected with enantiomerically pure ( R2R) rrfl/js-cyclohexane diol (see Table 4, entry 7). Addition of phenyl Grignard reagent, catalyzed by Cul, produced a moderate yield (50%) of a mixture of the two diastereomers (prochiral carbon R/5 = 78% 22%) with a d.e. of 55%. In contrast, the authors also reported that addition of the phenyl lithium cuprate gave 94 6 ratio with the major product having the S-configuration for the prochiral carbon. Because of the differences in the structures of the complexes, attack from the lithium cuprate comes from the Re-face, whereas attack from the copper-Grignard comes from the Si-face. 

The major cause of difficulty in achieving stereoselectivity in free radical reactions lies within the nature of the prochiral carbon-centred radical. Experimental evidence suggests that prochiral radicals are almost planar and essentially sp2 hybridised, with the unpaired electron occupying an unhybridised p-orbital located perpendicular to the plane of substitution (Figure 7.1).30... 

As the term amino acid describes, each monomer has an amine group and a carboxylic acid group attached to a prochiral carbon. In addition side chains can also be present. These range from a simple hydrogen to long carbon chains with functional groups. 

Raney nickel, modified by free tartaric acids 2.69 (R = H) or their salts, has frequently been used as a catalyst for asymmetric hydrogenations of carbonyl compounds [578,948]. Several industrial applications have been described [578, 811, 812], Neveriess, hydrogenations of prochiral carbon-carbon double bonds in the presence of such catalysts gives disappointing results [578], The use of tartrate-modified copper catalysts in cyclopropanation of styrenes by diazoketones takes place with a modest asymmetric induction [578,936]. 

Optically active silanes were obtained from symmetrical ketone, RCOR, in up to 46% enantiomeric excess, the catalyst being the only source of chirality. Asymmetric induction was also observed at the prochiral carbon of constitutionally unsymmetrical ketones, RCOR The optical yield at the carbon atom is different from that at silicon. This is well understood on the basis of kinetic Scheme 13. The diastereomeric complexes 56 and 57 interconvert rapidly in solution. Each complex reacts with different rates at the two faces (a and 0) of the ketone. The optical purity at the silicon center depends on the relative rates of... 

Optically active silanes were obtained from symmetrical ketones RCOR, in up to 46% enantiomeric excess, the catalyst being the only source of chirality. Asymmetric induction was also observed at the prochiral carbon of constitutionally unsymmetrical ketones ... 

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